risk/benefit evaluation in fih trials: implications for gene editing in human embryos jonathan...
TRANSCRIPT
Risk/Benefit Evaluation in FIH Trials:
implications for gene editing in human embryos
Jonathan KimmelmanBiomedical Ethics / Experimental MedicineMcGill University
risk
benefit
?
part 1: overview
part 2: framework
part 3: extending to embryos
part 1: overview
2
1) prior evidence
2) trial design
(1) (2)
risk Benefit:a) subjects +b) society
clinical promise
part 2: framework
2
1. animal efficacy evidence
treatmt effect
ANIMAL
treatmt effect
ANIMAL
effect
HUMAN
treatmt
treatmt effect
ANIMAL
a)
treatmt effect
ANIMAL
treatmt effect
ANIMAL
treatmt effect
ANIMAL
treatmt effect
ANIMAL
treatmt effect
ANIMAL
treatmt effect
ANIMAL
treatmt effect
ANIMAL
treatmt effect
ANIMAL
treatment “generalizable” effect
noisebias
cause specific effect
b)
treatment effect
animal
confound
treatment effect
animal
treatment effect
human
cause effect cause effect
human
cause effect
cause effect
context specific
PLoS Medicine 2013
2. clinical evidence
reference class
Dementia
amyloid precursor protein
b-secretase
g-secretase
Aß
Aß
X
Source: Kimmelman J, London AJ, PLoS Med 2010
¯ confidence
treatmt effect
HUMAN
a)
treatmt effect
HUMAN
treatmt effect
HUMAN
treatmt effect
HUMAN
treatmt effect
HUMAN
treatmt effect
HUMAN
treatmt effect
HUMAN
treatmt effect
HUMAN
treatmt effect
HUMAN
b)
p(RC)
PLoS Medicine 2011
b)
p(Effrc) x p(Effpc)
3. moral evaluation
- risk / benefit- direct social
value- fecundity…
part 3: extending to embryos
4
1. safety, not efficacy
2. reference class
1st generation:integrating vectors into pluripotent cells?
3. identity
4. long tail
EVENT RATE
p(E)
p(E)